This grant addresses how time coding arises during the development of the auditory system, and how this timing information is preserved and improved in the CNS. The analysis of temporally ordered inputs is integral to processing both sound location information and communication signals such as speech. Mechanisms of time coding may be particularly accessible in the bird's auditory brainstem. In birds, auditory nerve fibers enter the brain and divide to terminate in the cochlear nucleus angularis and the cochlear nucleus magnocellularis. The projection from the nucleus magnocellularis to the nucleus laminaris supports the encoding and measurement of interaural time differences. In the nucleus laminaris, the magnocellular axons form delay lines to create maps of interaural time differences which are tapped by postsynaptic coincidence detectors. During the first few weeks of life, the young bird's head more than doubles in size, subjecting it to changing interaural cues. The myelination of the magnocellular delay lines within the nucleus laminaris occurs late in development, during this period of maximum head growth. Since the late myelination of the delay line circuit is functionally significant, we will examine the developmental profile of myelin genes and the factors that regulate their expression in the brainstem auditory nuclei. We will compare the timing of this gene expression with the physiological and anatomical maturation of the delay line circuit. In parallel with the studies of myelination, we will also examine the development of time coding during the tuning and assembly of the map of interaural time differences. The neurons in the nucleus magnocellularis and laminaris encode the timing of the auditory stimulus. We will determine how this time coding develops. In the adult bird, nucleus laminaris neurons are maximally excited by simultaneous activation of their ipsi- and contralateral inputs, via a coincidence detection mechanism. Since the timing of the presynaptic inputs is critical to coincidence detection, we will determine when the "correct" timing of the inputs is achieved. The mechanism underlying the tuning of these inputs is of general interest, since many models of development depend upon selection of temporally ordered inputs. We will describe the development of synaptic inputs to the auditory brainstem. GABAergic inputs will be examined to determine if the development of the inhibitory projections parallels the development of the ascending auditory projections. The expression of glutamate receptors in the auditory brainstem will be analyzed to determine if dendritic growth is correlated with changes in receptor expression in the nucleus magnocellularis and the nucleus laminaris.